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Ishino, Mikimasa. "The Xin ming of the founder of the Niutou sect Farong chanshi and the Xinxin ming of the third master Sengcan: On the Philosophies in the Formative Period of Chan Thought." Journal of Indian and Buddhist Studies (Indogaku Bukkyogaku Kenkyu) 67, no. 2 (March 20, 2019): 844–41. http://dx.doi.org/10.4259/ibk.67.2_844.
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Lowie, Kathryn. "Xin bian Ming ren nianpu congkan." Ming Studies 2001, no. 1 (January 2001): 144–50. http://dx.doi.org/10.1179/014703701788763080.
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Stezhenskaya, L. V. "Kowalewski Apropos the Chinese Book “Ming Xin Bao Jian”: Following up a Diary Entry." Vestnik NSU. Series: History and Philology 22, no. 10 (December 23, 2023): 77–88. http://dx.doi.org/10.25205/1818-7919-2023-22-10-77-88.
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This article examines the notes of the prominent Russian mongolist of Polish origin Józef Kowalewski (1801–1878) in his “Diary of studies for 1832”, the manuscript of which is kept in the Department of Manuscripts of the Vilnius University Library. This diary entry has been previously published several times in the form of a facsimile. It is an excerpt in English from the annotation on the Chinese book Ming xin bao jian (明心寶鑑, Precious Mirror for the Enlightenment of the Mind) from the Protestant missionary magazine published in Malacca. The article clarifies and significantly supplements the previously published commentary on this entry, defines The Indo-Chinese Gleaner magazine as the source of the English annotation and William Milne (1785–1822) as its author. It is assumed that J. Kowalewski’s acquaintance with W. Milne’s note had determined later choice of Ming xin bao jian as a Chinese language teaching material at The Imperial Kazan University. The very fact of choosing this book by a Protestant missionary to be presented as an important manual on the Chinese language and the traditional worldview of the Chinese is discussed. The conclusion is made that, formally remaining in opposition to the earlier Catholic missionary work, Protestant preachers in assessing Ming xin bao jian were in consent with their predecessors.
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Wang, Zhen-xin, Xi-long Feng, Chengwei Liu, Jin-ming Gao, and Jianzhao Qi. "Correction: Wang et al. Diverse Metabolites and Pharmacological Effects from the Basidiomycetes Inonotus hispidus. Antibiotics 2022, 11, 1097." Antibiotics 11, no. 11 (November 21, 2022): 1671. http://dx.doi.org/10.3390/antibiotics11111671.
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In the original publication, there were publisher errors in the names of authors Zhen-xin Wang, Xi-long Feng and Jin-ming Gao and affiliation (1) of the first, second, fourth and fifth authors (name of the Key Laboratory and city) [...]
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Wang, Lele. "A Study of the Gansu Official Hu Xin and his Collection Yu Fen Cao in Microcosmic Perspective." Journal of Social Science Humanities and Literature 6, no. 6 (December 29, 2023): 65–69. http://dx.doi.org/10.53469/jsshl.2023.06(06).11.
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Hu Xin was a famous official in Tianshui, Gansu during the Wanli period of the Ming Dynasty. He served in several branches of the central government, and his highest official position was that of the Supreme Leader of the Taichang Temple. Hu Xin's collection, Yu Fen Cao, documents his many initiatives to serve the people, impeach corrupt officials, and maintain national stability during his tenure. It reflects well on his political ambitions. Analyzing Hu Xin's historical contribution to the country and the people and his positive influence, we can further enrich the historical image of Hu Xin, and also provide historical details for understanding the prosperity and demise of the Donglin Party.
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Xiaozhong, Teng. "The occurrence and development of traditional Chinese painting of the regional Xin Jinling school and its prominent representatives." Bulletin of Lviv National Academy of Arts, no. 51 (October 10, 2023): 134–45. http://dx.doi.org/10.37131/2524-0943-2023-51-13.
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This article explores the emergence and development of the Xin Jinling school of traditional Chinese painting, focusing on its notable representatives. The main objective of this study is to investigate the school's formation, development, and the artistic features of works by renowned artists such as Fu Baoshi, Qian Songyan, Ya Ming, Wei Zixi, and Song Wenzhi. The scientific novelty of this research resides in determining the role and significance of the regional Xin Jinling school in Chinese art history and assessing its influence on contemporary Chinese art. Employing research methods such as historical and iconographic analysis, a historical and biographical approach, formal and stylistic analysis, and comparative analysis, the study delves into the school's main representatives. This article examines the geographical and chronological scope of the Xin Jinling school while elucidating the historical, sociopolitical, and cultural contexts of its formation. It also outlines the school's development trajectory, significantly impacted by China's political landscape during the twentieth century. Furthermore, the article scrutinizes the creative paths and artistic attributes of the school's primary representatives, analyzing the commonalities and distinct features of their works. These artists captured the spirit of their time and the everyday lives of the people, demonstrating a profound appreciation for nature. They devoted considerable attention to plein air activities, with each artist employing a unique creative approach. In conclusion, this article underscores the importance of the Xin Jinling school within the annals of Chinese art history. The findings of this research enhance our understanding of contemporary Chinese art by studying the Xin Jinling school of traditional painting as an integral component of China's artistic heritage.
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Breach, D. R., C. Krattenthaler, and Marcus Schorn. "Two Combinatorial Identities (Ma Xin-Bong and Wang Tian-Ming)." SIAM Review 38, no. 1 (March 1996): 148–52. http://dx.doi.org/10.1137/1038013.
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LENKOV, PAVEL D. "BUDDHIST ELEMENTS OF THE ANTHROPOLOGICAL CONCEPTIONS OF THE RELIGIOUS TAOISM OF THE QUANZHEN SCHOOL (BASED ON LONG MEN XIN FA): PSYCHOLOGY AND SOMATOLOGY." Study of Religion, no. 2 (2021): 44–55. http://dx.doi.org/10.22250/2072-8662.2021.2.44-55.
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The article deals with the analysis of anthropological concepts of one of the main schools of religious Taoism - Quanzhen / Longmen - in the aspect of identifying and considering the Buddhist elements of late Taoist anthropology. The main source for the analysis was the text of the 17th century Lun men xin fa (“The Law of the Heart-Consciousness [according to the Tradition] Longmen”), which outlined the views of Wang Changyue, master of the Taoist school Quanzhen / Longmen. The article examines the Buddhist elements of the late Taoist somatology and psychology: the concept of the heart-consciousness ( xin ), the concept of “vitality of wisdom” ( hui ming ), the doctrine of the “true spirit” ( zhen ling , yuan shen ). The central concept of the text - heart-consciousness - is interpreted by Wang Changyue to a large extent in a Buddhist way. Such concepts as the material body ( se shen ) and the Body of the Law ( fa shen ) are discussed in the text in the spirit of late Buddhist Mahayana psychology...
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Myoungseok Seo. "Gongfu Method viewed through Toegye’s Mindfulness: Based on Tian Ming Xin Tu." Journal of Educational Idea 30, no. 4 (November 2016): 95–109. http://dx.doi.org/10.17283/jkedi.2016.30.4.95.
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HAW, STEPHEN G. "The History of a Loyal Heart (Xin shi): a late-Ming forgery." Journal of the Royal Asiatic Society of Great Britain & Ireland 25, no. 2 (October 23, 2014): 317–25. http://dx.doi.org/10.1017/s1356186314000686.
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AbstractThe History of a Loyal Heart (Xin shi) is allegedly a work by the Song loyalist, Zheng Sixiao, written to bemoan the fate of the Song empire after its conquest by the Mongols. There have always been doubts about its authenticity, however, and many scholars have believed it to be a forgery. The arguments for and against this have remained inconclusive, and the work has been commonly used as a source for the history of the Song–Yuan transition period. This article adduces compelling evidence to show that there can be very little doubt that it is a late-Ming forgery. Some of the implications of this conclusion are briefly addressed.
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陳韻, 陳韻. "《春秋》微言在《新列國志》中的移轉表現淺說." 中正漢學研究 37, no. 37 (June 2021): 157–94. http://dx.doi.org/10.53106/2306036020210600370006.
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<p>處於銜接傳統與現代交替關鍵的明朝時期，人文風景展示著種種轉換的影像，或顯或隱，不論內涵與形式，都在巨細之間透露出相互呼應的消息，尤其是最能反映各類情境的通俗文學，不但吞吐即時訊息，而且提供背景資料，以及追蹤指南。因此，本論文擬連結儒家經典與通俗文學二者，探討傳統思維在時空易移下的吸納與演化。茲以精研《春秋》的「三言」（《喻世明言》、《警世通言》、《醒世恒言》）作者馮夢龍為關注主體，從轉變的角度，結合時代特質、學術取向、社會樣貌、文本體式、生命情理等多重層面，觀察其所撰《新列國志》之中，承載《春秋》的狀態，並尋繹其脈絡與意涵。</p> <p> </p><p>The Ming Dynasty was an era of alternating tradition and modernity. Popular literature was becoming more and more popular, and Feng Meng-long’s Xin Lie Guo Zhi is one of the representatives. This thesis will take Xin Lie Guo Zhi and Confucian classics Chun Que as examples to discuss the acceptance of Confucian thinking in popular literature at that time. The content includes: analysis and comparison of the characteristics of the times, social influence, writing characteristics, and humanistic care of Chun Que and Xin Lie Guo Zhi in angles of historical events, academic development, and literary performance.</p> <p> </p>
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Li, Xiaorong. "Where Have All the Guixiu Gone? Chinese “Women of Talent” at the Turn of the Twentieth Century." Journal of Chinese Literature and Culture 10, no. 1 (April 1, 2023): 81–107. http://dx.doi.org/10.1215/23290048-10362392.
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Abstract Guixiu 閨秀 (cultivated gentlewomen of the inner chambers) and cainü 才女 (women of talent) arguably became authorly identities (referring to women writing in classical verse) as women's literary culture took shape in Ming-Qing China. However, the guixiu and cainü were gradually eclipsed by their rising “modern” sisters, xin nüxing 新女性 (new women) and nü zuojia 女作家 (women writers), during the late-Qing reform (1890s) and the early-Republican New Culture movement (1910s–1920s). This study provides a historical investigation into two cases of the literary practice of men and women who carried the legacy of their Ming-Qing predecessors into the Republican era: Wang Wenru 王文濡 (1867–1935) and his Xiangyan zazhi 香艷雜誌 (Xiangyan Magazine, 1914–1916) and Gu Xianrong 顧憲融 (1901–1955), who published the Hongfan jingshe nü dizi ji 紅梵精舍女弟子集 (Collection of Female Disciples from the Abode of Red Brahman, 1928). They reveal the persistence of guixiu culture in a diversified and transformed world of literary production and consumption from the 1910s to the 1920s.
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Moon, Sang-leun. "Changes in the Iconography of the Attributes in the Thousand-handed Avalokiteśvara Paintings According to Scriptural Bases : Focusing on the Iconographies from the Tang to the Ming Dynasty." Korean Journal of Art History 315 (September 30, 2022): 245–76. http://dx.doi.org/10.31065/kjah.315.202209.008.
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Following the introduction and spread of scriptures of the Thousand-handed and Thousandeyed Avalokiteśvara bodhisattva in China, around seventy paintings of Thousand-handed Avalokiteśvara were produced since the late Tang period. There exist numerous studies on the attendants of the Thousand-handed Avalokiteśvara in different types of paintings, but the attributes of the bodhisattva have not been considered in depth.</br>Therefore, I have analyzed how the attributes of the Thousand-handed Avalokiteśvara were described in the canonical scriptures—namely, Qianshou qianyan Guanshiyin pusa guangda yuanman wuai dabei xin tuoluoni jing(千手千眼觀世音菩薩廣大圓滿無礙大悲心陀羅尼經), translated by Bhagavaddharma, Qianshou qianyan Guanshiyin pusa dabei xin tuoluoni(千手千眼觀世音菩薩大悲心陀羅尼) and Shewuai dabeixin da tuoluoni jing(攝無礙大悲心大陀羅尼經), both translated by Amoghavajra, and Qianguangyan Guanzizai pusa mimi fa jing(千光眼觀自在菩薩祕密法經) translated by Sanmeisupoluo(三昧蘇嚩羅),—and categorized the paintings by the scriptures they were based on. By studying nineteen paintings made in the period from the Tang to the Ming Dynasty, whose attributes could be clearly discerned, I discovered that the differences in the attributes depicted in the paintings are neither temporal nor geographical, but resulted from the base scriptures.</br>Conclusively, this study is significant as it proposes a new criterion for the study of the Thousand-handed Avalokiteśvara iconography.
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Li, Jinglin. "The ontologicalization of the Confucian concept of Xin Xing: Zhou Lianxi’s founding contribution to the Song-Ming Neo-Confucianism." Frontiers of Philosophy in China 1, no. 2 (June 2006): 204–21. http://dx.doi.org/10.1007/s11466-006-0003-x.
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Loewe, Michael. "Ban Gu: copyist, creator and critic." Bulletin of the School of Oriental and African Studies 78, no. 2 (February 17, 2015): 333–55. http://dx.doi.org/10.1017/s0041977x14001104.
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AbstractBan Gu's compilation of the Han shu may be seen in the context of a number of intellectual and religious developments. By his time the idea of the Tian ming and the theory of the Wu xing were being applied to imperial times. Officials were quoting the sayings of Kongzi to support their arguments, and the writings of distinguished scholars such as Jing Fang, Liu Xiang, Liu Xin and Yang Xiong were well known. The religious controversies that had begun in the reign of Chengdi had died down. The pursuit of scholarship had received a new impetus thanks partly to the discussions held in 79 ce. Ban Gu drew somewhat freely on existing literature, being prudent to select material that would not arouse enmity; his sister called on official documents to complete her part of the history. As an innovator Ban Gu introduced chapters on subjects that had not been treated in the Shi ji, such as bibliography and the laws. Ready to criticize the actions of officials or the character of an emperor openly, he also contrived to do so implicitly.
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Kim, Sookhyang. "Experiencing Literature in the Metaverse: Focusing on the design of Chinese classical prose class." Institute of Humanities at Soonchunhyang University 42, no. 1 (March 30, 2023): 121–45. http://dx.doi.org/10.35222/ihsu.2023.42.1.121.
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This study explores the use of the Metaverse platform ZEP as a novel teaching and learning method for Chinese classical prose education in universities. In today's technological society, Chinese classical prose has excellent educational value but is not fully utilized. This study identified the biggest problem of current Chinese classical prose education as the lack of interest among learners and introduced the Metaverse platform on a trial basis to supplement traditional teaching methods. The Metaverse platform focused on in this study is the ZEP, which was created with Korean technology. The study selected the work ｢Hu xin ting kan xue(湖 心亭看雪)｣ of Zhang Dai(張岱), a late Ming dynasty Xiaopin(小品) that fits the space and volume of work. The same mechanism as the appreciation through text reading was used in this paper to implement the work in the ZEP space. This study aims to arouse learners’ curiosity, interest, and even fun by utilizing innovative tools in teaching and learning Chinese classical prose. From this, the significance of the study can be found in enhancing learners’ engagement with Chinese classical prose.
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Shiu, Cao. "PIANO SUITE DU MING XIN «MERMAID» AS AN EXAMPLE OF THE COMBINATION OF THE PRINCIPLES OF NATIONAL AND EUROPEAN MUSICAL LANGUAGE." Ukrainian music 32, no. 2 (December 4, 2019): 98–104. http://dx.doi.org/10.33398/2224-0926-2019-32-2-98-104.
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Shiu, Cao. "PIANO SUITE DU MING XIN «MERMAID» AS AN EXAMPLE OF THE COMBINATION OF THE PRINCIPLES OF NATIONAL AND EUROPEAN MUSICAL LANGUAGE." Ukrainian music 32, no. 2 (December 2019): 98–104. http://dx.doi.org/10.33398/2224-0926-2019-32-2/98/104.
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Sun, Shuang, Li Liang, Ming Li, and Xin Li. "Erratum for “Bridge Performance Evaluation via Dynamic Fingerprints and Data Fusion” by Shuang Sun, Li Liang, Ming Li, and Xin Li." Journal of Performance of Constructed Facilities 34, no. 1 (February 2020): 08219002. http://dx.doi.org/10.1061/(asce)cf.1943-5509.0001324.
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Xiao, Yin. "Juan Cobo’s Thoughts on the Chinese–Occidental Cultural Integration." Religions 13, no. 12 (December 1, 2022): 1168. http://dx.doi.org/10.3390/rel13121168.
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Juan Cobo, a Spanish Dominican, preached to the Chinese in the Philippines between 1588 and 1592. During this time, he translated Ming Xin Bao Jian 《明心寶鑒》, which was the first Chinese classic translated into a Western language. In addition, he also authored an evangelical work: Bian Zheng Jiao Zhen Chuan Shilu 《辯正教真傳實錄》. His approach was notably different from his contemporary Dominicans’ orthodox inclinations. Juan Cobo’s works show his enthusiastic admiration for the Chinese culture, which is demonstrated in his open attitude towards the Confucian and Daoist doctrines, as well as in his recorded egalitarian discussion with a Mandarin scholar. In this article, based on Juan Cobo’s works, an analysis is undertaken regarding how this missionary adopted Neo-Confucian concepts and ideas, which then occupied a mainstream position in the local academic world, in his evangelical work with the Chinese people. Furthermore, this analysis also investigates how Juan Cobo intended to integrate the Oriental and Western philosophies, despite their theoretical and methodological divergences, in order to achieve the quick acceptance and diffusion of Christianity among the Sangleys. The historical background, the causes, and the results of such practices are also discussed in the present article.
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Moss, Robert L., Robert E. Flynn, Xin-Ming Shen, Carol Dudley, Jiming Shi, and Milos Novotny. "Urine-Derived Compound Evokes Membrane Responses in Mouse Vomeronasal Receptor Neurons." Journal of Neurophysiology 77, no. 5 (May 1, 1997): 2856–62. http://dx.doi.org/10.1152/jn.1997.77.5.2856.
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Moss, Robert L., Robert E. Flynn, Xin-Ming Shen, Carol Dudley, Jiming Shi, and Milos Novotny. Urine-derived compound evokes membrane responses in mouse vomeronasal receptor neurons. J. Neurophysiol. 77: 2856–2862, 1997. Sensory neurons of the vomeronasal organ (VNO) are thought to detect species-specific chemical signals important for reproductive function. The electrical properties of VNO neurons have begun to be characterized in a variety of species; however, the response of VNO neurons to possible physiological ligands has not yet been reported. One physiological effector, dehydro-exo-brevicomin (DHB), is found in the urine of intact male mice and affects the estrous cycle of female mice. In the present study, dissociated VNO neurons were voltage- or current-clamped and their response to DHB was determined. Approximately 26% of VNO neurons responded to DHB with an outward current at negative holding potentials; the current reversed at approximately +4 mV. Application of DHB in current-clamp mode produced membrane hyperpolarization and/or a reduction in the firing of action potentials. Because membrane conductance was shown to be decreased during application of DHB, the results suggest that the outward current associated with DHB application is a reflection of a reduction in inward current caused by closing an ion channel. This study provides the first evidence that a compound found in male urine directly affects VNO neurons.
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Chen, Wanyi, Yufeng Wang, Liangliang Ji, Ming O. Li, and Xin-Yun Huang. "Abstract 4960: Fascin inhibitor decreases gynecological cancer cell growth through cell cycle regulation." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4960. http://dx.doi.org/10.1158/1538-7445.am2023-4960.
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Abstract The actin cytoskeleton is essential for maintaining cell morphology and architecture. Actin-bundling proteins such as fascin cross-link actin filaments into bundles and play critical roles in regulating cell protrusion and motility. Fascin protein expression is low or absent in normal human epithelial cells but high in cancer cells. Elevated fascin levels are correlated with aggressive clinical progression, poor prognosis, and shorter survival outcomes. It is regarded as a cancer progression biomarker and a therapeutic target. We have developed a small molecule fascin inhibitor and shown its efficacy in blocking tumor cell migration, invasion, and metastasis, as well as prolonging the overall survival of mice bearing different types of cancers. Our recent data reveals a new mechanism of this fascin inhibitor in cell cycle regulation of gynecological cancer cells. It blocks the G2/M progression and decreases the mitotic index. Fascin inhibitor treatment also results in aneuploidy, which is a well-known factor for triggering downstream apoptosis. Our data suggests that fascin is involved in maintaining the fidelity of chromosome segregation and cell division. This will advance our understanding of the interplay between actin and microtubule cytoskeleton during cell mitosis. Citation Format: Wanyi Chen, Yufeng Wang, Liangliang Ji, Ming O. Li, Xin-Yun Huang. Fascin inhibitor decreases gynecological cancer cell growth through cell cycle regulation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4960.
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Mak, Celia Sze Ling, Ming Zhu, Xin Liang, Feng Wang, Anh G. Hoang, Xinzhi Song, Peter Shepherd, et al. "Abstract 4760: KDM4A promotes NEPC progression through regulation of MYC expression." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4760. http://dx.doi.org/10.1158/1538-7445.am2023-4760.
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Abstract Despite advancements in treatment, prostate cancer (PCa) remains the second leading cause of death among men. Neuroendocrine prostate cancer (NEPC) represents one of the most lethal forms of PCa and lacks life-prolonging treatment. Here we identified histone lysine demethylase KDM4A as a driver in NEPC progression and an effective therapeutic target. KDM4A mRNA and protein are overexpressed in human and mouse NEPC compared to adenocarcinoma. Knockdown or knockout of KDM4A in NEPC cell lines suppressed cancer cell growth in vitro and in vivo. Importantly, the inactivation of Kdm4a in a genetically engineered mouse model of prostate cancer reduces tumor burden, reduces the incidence of NEPC, and prolongs overall survival. Mechanistically, KDM4A directly regulates the transcription of MYC, which is hyper-activated in human and mouse NEPC. Furthermore, a potent pan-KDM4 inhibitor QC6352 significantly reduces NEPC cell growth in vitro and in vivo. Taken together, we demonstrate that KDM4A promotes NEPC progression through regulation of MYC expression and targeting KDM4A can be an effective therapeutic strategy for NEPC. Citation Format: Celia Sze Ling Mak, Ming Zhu, Xin Liang, Feng Wang, Anh G. Hoang, Xinzhi Song, Peter Shepherd, Derek Liang, Jessica Suh, Jiwon Park, Miao Zhang, Eric Metzger, Roland Schule, Abhinav K. Jain, Ellen Karasik, Barbara A. Foster, Min Gyu Lee, Paul Corn, Christopher J. Logothetis, Ana Aparicio, Nora Navone, Patricia Troncoso, Jianhua Zhang, Sue-Hwa Lin, Guocan Wang. KDM4A promotes NEPC progression through regulation of MYC expression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4760.
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Zhu, Chen, and Xin-Yuan Liu. "Cluster Preface: Radicals – by Young Chinese Organic Chemists." Synlett 32, no. 04 (February 16, 2021): 354–55. http://dx.doi.org/10.1055/s-0040-1706715.
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(left) received his B.S. degree from Xiamen University in 2003 under the supervision of Prof. Pei-Qiang Huang, and his Ph.D. degree from the Shanghai Institute of Organic Chemistry in 2008 under the supervision of Prof. Guo-Qiang Lin. After postdoctoral research at Gakushuin University, Japan with Prof. Takahiko Akiyama, he moved to the University of Texas Southwestern Medical Center, working as a postdoctoral fellow with Prof. John R. Falck and Prof. Chuo Chen. He was appointed as a professor at Soochow University, China in December 2013. He is currently the Head of the Organic Chemistry Department at Soochow University. His current research interests include radical-mediated transformations, in particular radical rearrangements, and their applications in the construction of natural products and biologically active compounds. Xin-Yuan Liu (right) obtained his B.S. degree from Anhui Normal University (AHNU) in 2001. He continued his research studies at both the Shanghai Institute of Organic Chemistry (SIOC), CAS and AHNU under the joint supervision of Prof. Dr. Shizheng Zhu and Prof. Dr. Shaowu Wang, obtaining his master’s degree in 2004. After a one-year stint in Prof. Gang Zhao’s laboratory at SIOC, he joined Prof. Dr. Chi-Ming Che’s group at The University of Hong Kong (HKU) and earned his Ph.D. degree in 2010. He subsequently undertook postdoctoral studies in Prof. Che’s group at HKU and in Prof. Carlos F. Barbas III’s group at The Scripps Research Institute. At the end of 2012, he began his independent academic career at the Southern University of Science and Technology (SUSTech) and was promoted to a tenured Full Professor of SUSTech in 2018. His research interests are directed towards the design of novel chiral anionic ligands to solve radical-involved asymmetric reactions.
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Belaya, Irina. "Song of the Great Dao of the Spiritualized Source: Preliminary Study." Voprosy Filosofii, no. 5 (July 2024): 178–89. http://dx.doi.org/10.21146/0042-8744-2024-5-178-189.
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The article is devoted to the study of the Song of the Great Dao of the Spiritualized Source (Ling yuan da dao ge). This is a work on Daoist “inner alchemy”, which describes the process of transforming the spirit and the breath in poetic form. The author of Ling yuan da dao ge was the Daoist nun and poetess Cao Wen-yi (1039–1115). Cao Wen-yi is the only woman-philosopher who wrote a commentary on the Dao De jing, which has survived to this day in the Daoist Canon (Dao zang). Her talents were highly appreciated by Emperor Huizong, who granted her the title “Excellent in Literary Talent” (Wen-yi zhen-ren). The goal of the study is to highlight the most important ideological and theoretical components of the Song of the Great Dao of the Spiritualized Source. As a result of the study, the cultural and historical environment of this work was reconstructed, its earlier list written in prose was identified, the dating of the full version of Ling yuan da dao ge was clarified, and its content features were revealed. The main task of the Song of the Great Dao of the Spiritualized Source is to explain the principle of simultaneous improvement of inner nature and vitality (xing ming shuang xiu). This principle became the main vector of development of Daoist psychophysiological methods, starting from the Song era. Improving the inner nature, according to Cao Wen-yi, is achieved by detaching the heart from feelings and desires. This state is called “no heart” (wu xin) and is the “true heart of the Dao”. Improving vitality is achieved through breathing exercises, which should be based on the principles of suchness (zi ran) and non-action (wu wei).
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Wang, Fuhao, Yu He, Xin Huang, Ming Chang, Xiao Zhang, Xiaoyi Li, Xinyu Ye, and Yi Lu. "Abstract 2752: ICA1 promotes prostate cancer progression and metastasis via AR down-regulation." Cancer Research 84, no. 6_Supplement (March 22, 2024): 2752. http://dx.doi.org/10.1158/1538-7445.am2024-2752.
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Abstract Cancer metastasis, one of the main characteristics in malignancy, contributes to high mortality in cancer patients. Prostate cancer (PCa) is the most common cancer among men and the second leading cause of cancer-related death in Europe and the United States. In China, its incidence has been dramatically increased over past years. However, the mechanism of PCa progression and metastasis remains unclear. The androgen receptor (AR) has been demonstrated to play an important role in PCa progression and metastasis. We have previously established mouse models of PCa bone metastasis and PCa lung metastasis. We have obtained cell clones with bone-specific or lung-specific metastatic capability. By transcriptomic analysis of highly metastatic cell clones and their parental cells, we found a gene group including islet cell autoantigen 1 (ICA1) that are highly expressed in both metastatic cell clones. We further compared these results with RNA array data in clinical samples. Data comparison and correlation analysis showed that ICA1 was negatively correlated with AR expression. Survival analysis of PCa and lung cancer patients showed higher expression of ICA1 but with shorter overall survival. Down-regulation of ICA1 expression in highly metastatic tumor cells significantly inhibited cell growth, colony formation, migration, and invasion. ICA1 overexpression in parental RM1 cells apparently increased cell growth, migration, and metastasis. Interestingly, down-regulation of ICA1 also significantly activated AMPK/mTOR signaling pathway. These findings are anticipated to shed light on the novel pathogenic mechanism underlying PCa and propose a compelling theoretical basis for the application of ICA1 in PCa. This work supported by the NSFC projects (81972420, 81972766, 82173336), as well as grants from the Science and Technology Project of Shenzhen (JCYJ20210324104214040, JCYJ20190809161811237).Keywords: prostate cancer, metastasis, ICA1, androgen receptor Citation Format: Fuhao Wang, Yu He, Xin Huang, Ming Chang, Xiao Zhang, Xiaoyi Li, Xinyu Ye, Yi Lu. ICA1 promotes prostate cancer progression and metastasis via AR down-regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2752.
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Meng, Jie, Ming Chang, Siyuan Qin, Xin Huang, Weiping Liang, Haibo Tong, and Jian Zhang. "Abstract 5387: Host-derived CCL2 drives prostate cancer bone metastasis via CCND2/STAT3 pathway." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5387. http://dx.doi.org/10.1158/1538-7445.am2024-5387.
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Abstract Overexpression of tumor-derived CCL2 has been shown to partially promote prostate cancer (PCa) bone metastasis, but the function of host-derived CCL2 is not fully understood. We first developed a mouse model using intracardiac injection and obtained highly metastatic PCa cell subclones through in vivo selection. The highly metastatic tumor cells were injected intracardially into CCL2 knockout (CCL2 KO) mice and wild-type (WT) controls, and the tumor cell growth and metastasis were monitored weekly by bioluminescence imaging. The osteolytic lesions were evaluated by radiography, micro-computed tomography (microCT) and immunohistochemistry (IHC) staining. The cells in the bone microenvironment were analyzed by flow cytometry. Also, RNA sequencing (RNA-seq) analysis was performed on the cells either from CCL2 KO mice or WT controls. We found that a loss of host-derived CCL2 significantly retarded tumor growth in bone and prolonged mouse survival. In addition, bone density analysis revealed a decrease in osteolytic lesion in CCL2 KO mice, compared to WT controls. Systemically, CCL2 deficiency reduced the proportion of granulocyte-myeloid-derived suppressor cell (G-MDSC) populations with immunosuppressive function and decreased the PCa conditioned medium (CM)-induced osteoclast formation. The enrichment analysis revealed that the dysregulated genes in bone metastatic cells from CCL2 KO mice were significantly enriched in several biological processes, including vitamin metabolism, monoatomic anion homeostasis, immune response, and bone growth. Additionally, we also confirmed that the CCND2/STAT3 pathway is apparently suppressed in the cells from CCL2 KO mice. This study demonstrated that targeting the host-derived CCL2 might be a novel potential anti-metastatic approach. Supported by the NSFC projects (81972766, 81972420, 82173336), as well as grants from the Science and Technology Project of Shenzhen (JCYJ20190809161811237, JCYJ20210324104214040). Key words Host-derived CCL2; Prostate cancer; Bone metastasis; osteoclast; CCND2 Citation Format: Jie Meng, Ming Chang, Siyuan Qin, Xin Huang, Weiping Liang, Haibo Tong, Jian Zhang. Host-derived CCL2 drives prostate cancer bone metastasis via CCND2/STAT3 pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5387.
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Lu, Jiajun, Ming Gao, Hao He, Lijian Feng, Zhenting Gao, Wenqi Cui, Kun Yang, et al. "Abstract 1671: Discovery of ETS-003, a potent and selective YAP/TAZ-TEAD PPI inhibitor with broad anti-tumor activity in Hippo-YAP aberrant cancers." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1671. http://dx.doi.org/10.1158/1538-7445.am2023-1671.
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Abstract Hippo/YAP is a conserved signaling pathway controlling organ development, tissue regeneration and immune modulation. Cascade of tumor suppressor genes (NF2, LATS1/2) and multiple signals from cellular microenvironment (mechano-transduction) regulate YAP/TAZ phosphorylation and degradation. The stabilized YAP/TAZ translocate from cytoplasm to nucleus, where they bind with TEADs for transcriptional activation. YAP/TAZ regulate numerous genes expression which play central roles in cell proliferation, apoptosis, tumor microenvironment remodeling, and drug resistance, making them appealing targets for cancer treatment. Disruption of YAP/TAZ-TEAD protein-protein interaction (PPI) has been regarded as an effective approach to abolish YAP/TAZ oncogenic activity. Previously we have reported the discovery of YAP/TAZ-TEAD PPI hit compounds bound at the Ω loop site of TEAD1. Here we report that the CADD-guided optimization of the hit compounds has yielded an orally available and potent YAP/TEAD PPI inhibitor ETS-003 with favorable ADME properties and robust anti-tumor efficacy. ETS-003 could potently block YAP/TAZ-TEAD PPI both in vitro and in cells, and disrupt YAP/TAZ genome-wide chromatin binding, resulting in on-target inhibition of YAP transcriptome. ETS-003 exhibited broad anti-proliferative activity in a variety of solid tumor cell lines. In Hippo-YAP dysregulated mesothelioma models, ETS-003 showed profound anti-tumor activity and good PK/PD/efficacy correlation. Moreover, when combined with MAPK pathway inhibitors (Osimertinib, Sotorasib and MRTX1133), ETS-003 could significantly enhance the anti-proliferative activity, suggesting multiple combination opportunities for ETS-003 in clinical investigations. The non-GLP studies of ETS-003 showed favorable safety margin, and warranted further clinical studies of ETS-003 in solid tumors. Citation Format: Jiajun Lu, Ming Gao, Hao He, Lijian Feng, Zhenting Gao, Wenqi Cui, Kun Yang, Jiting Lu, Qiangang Zheng, Jidong Zhu, Xin Guo. Discovery of ETS-003, a potent and selective YAP/TAZ-TEAD PPI inhibitor with broad anti-tumor activity in Hippo-YAP aberrant cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1671.
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Chen, Li, Yi-Zhou Jiang, Songyang Wu, Jiong Wu, Genhong Di, Guangyu Liu, Keda Yu, et al. "Abstract P2-14-04: Updated data from FUTURE-C-PLUS: Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for advanced, immunomodulatory triple-negative breast cancer, an open-label, single-arm, phase 2 trial." Cancer Research 82, no. 4_Supplement (February 15, 2022): P2–14–04—P2–14–04. http://dx.doi.org/10.1158/1538-7445.sabcs21-p2-14-04.
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Abstract Background Camrelizumab and nab-paclitaxel demonstrated promising anti-tumour activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC) in FUTURE trial. Anti-angiogenic agents have been reported to facilitate immune infiltration. Famitinib is a tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit. The FUTURE-C-PLUS trial (NCT04129996) which added famitinib to camrelizumab and nab-paclitaxel is a single-arm, phase 2 trial evaluating this novel triplet combinatorial strategy in patients with advanced immunomodulatory TNBC. Study design and the primary endpoint ORR has been reported previously (Zhi-ming Shao, et al. ASCO 2021, Abstract 1007). Here, we reported the updated results of this trial. Method Briefly, this study enrolled women aged 18-70 years, with previously untreated, histologically confirmed, unresectable, locally advanced, recurrent or metastatic immunomodulatory TNBC. Immunomodulatory TNBC was defined as CD8 expression on at least 10% of cells using immunohistochemistry analysis. Eligible patients received the triple therapy. Study design has been reported previously in ASCO 2021. Results Between Oct 2019 and Oct 2020, 48 patients were enrolled and treated. 39 (81.3%, 95% CI 70.2-92.3) patients had a confirmed objective response which has been reported in ASCO 2021. At this updating data cutoff (June 30, 2021), the median progression-free survival was 11.9 months (95% CI, 7.3-16.5) with the median follow-up was 14.0 months. While overall survival data were not mature yet, a promising overall survival rate was observed at 12 months (84•2%, 95% CI 73.4-95.0) and 18 months (73.6%, 95% CI 52.0-95.2). In the 39 responders, median duration of response was also not mature. The disease control rate was 95.8% (46/48). The most common treatment-related grade 3 or 4 adverse events were neutropenia (16 [33.3%]), anemia (5 [10.4%]), febrile neutropenia (5 [10.4%]), and thrombocytopenia (4 [8.3%]). No treatment-related deaths were reported. Conclusions These data, combined with those from our previous reports, provide further evidence for the triplet combination of famitinib, camrelizumab and nab-paclitaxel as an active therapy in advanced Immunomodulatory TNBC. To our knowledge, this is the best objective response rate reached in first-line treatment of advanced TNBC. A randomized controlled FUTURE-Super trial (NCT04395989) is keeping recruiting patients to further validate those findings. Citation Format: Li Chen, Yi-Zhou Jiang, Songyang Wu, Jiong Wu, Genhong Di, Guangyu Liu, Keda Yu, Lei Fan, Junjie Li, Yifeng Hou, Zhen Hu, Canming Chen, Xiaoyan Huang, Ayong Cao, Xin Hu, Shen Zhao, Xiaoyan Ma, Xiaoyu Zhu, Jianjun Zou, Wentao Yang, Zhonghua Wang, Zhi-ming Shao. Updated data from FUTURE-C-PLUS: Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for advanced, immunomodulatory triple-negative breast cancer, an open-label, single-arm, phase 2 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-04.
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Ng, Kai Yu, Tsz-Lok Fong, Ya Gao, Tin-Lok Wong, Yuan Gao, Jing-Ping Yun, Xin-Yuan Guan, Ming Liu, Clive YS Chung, and Stephanie Ma. "Abstract 2429: AGPAT4 as a novel metabolic driver of oncogenic stemness and dedifferentiation in hepatocellular carcinoma." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2429. http://dx.doi.org/10.1158/1538-7445.am2023-2429.
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Abstract The liver is an unique organ in that it is responsible for many metabolic functions. During HCC development, these metabolic machineries are extensively reprogrammed to support the insatiable nutrient requirement of HCC. Cancer stem cells (CSCs) are a small and elusive subpopulation of self-renewing cancer cells with remarkable ability to initiate, propagate, and spread the malignant disease. Liver CSCs reprogram their metabolic pathways to match with the increased metabolic needs for cancer cell survival under adverse conditions. Identifying novel metabolic targets that are related to stemness can offer promising strategies for targeting CSCs and hence to kill and to control their growth. In this study, pathway enrichment analysis of genes that linked metabolism and stemness identified aberrant glycerophospholipid metabolism of which AGPAT4 ranked a top-hit. AGPAT4 upregulation in HCC is tightly correlated with aggressive clinical features, including survival, metastasis, and stemness signatures. Expression of AGPAT4 peaked during early liver progenitor development, decreased during hepatocyte maturation and increased progressively from well-differentiated to poorly differentiated HCCs. Enrichment of AGPAT4 in HCC was mediated by promoter binding of SOX9 to drive AGPAT4 transcriptional activity. AGPAT4 inhibition could mitigate tumor initiation, self-renewal, metastasis and sorafenib resistance. Mechanistic studies revealed an AGPAT4-mediated phosphatidic acid production axis to promote HCC through regulating mTOR signaling. Inhibition of Agpat4 by AAV8 shRNA reduced tumorigenicity and stemness, and sensitized HCC tumors to sorafenib. AGPAT4 overexpression was able to predict sorafenib response in the clinic. Through high-throughput screening coupled with activity-based protein profiling, a cysteine-reacting compound with high binding affinity and selectivity towards AGPAT4 was identified and found to work synergistically with sorafenib to supress HCC. To conclude, AGPAT4 is a novel metabolic driver of oncogenic stemness, dedifferentiation and metastasis in HCC. AGPAT4-induced tumor lineage plasticity may represent an Achilles heel for HCC. Inhibition of AGPAT4 may widen the therapeutic window for sorafenib treatment in the clinic. Citation Format: Kai Yu Ng, Tsz-Lok Fong, Ya Gao, Tin-Lok Wong, Yuan Gao, Jing-Ping Yun, Xin-Yuan Guan, Ming Liu, Clive YS Chung, Stephanie Ma. AGPAT4 as a novel metabolic driver of oncogenic stemness and dedifferentiation in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2429.
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Lin, Caijin, Xi Jin, Ding Ma, Chao Chen, Xin Hu, Yi-Zhou Jiang, and Zhi-Ming Shao. "Abstract PO1-15-02: Comprehensive characterization of genetic interactions in breast cancer reveals therapeutic vulnerabilities." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO1–15–02—PO1–15–02. http://dx.doi.org/10.1158/1538-7445.sabcs23-po1-15-02.
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Abstract Background: Genome-informed and genome-targeted precision treatment for breast cancer have achieved remarkable progress in improving clinical outcomes for patients with specific genetic alterations. However, treatment efficacy is compromised by the current practice of basing treatment decision-making solely on single driver alterations, without considering the role of genetic interactions. Consequently, it is of great necessity to conduct systematic investigations to determine the clinical relevance of genetic interactions. Methods: We established a large-scale multi-omics cohort (N=873) and a real-world clinical sequencing cohort (N=4,421) representing the Asian breast cancer population. Detailed treatment records were collected. We then investigated the prognostic and predictive effects of genetic interactions based on multivariate Cox proportional hazards model and logistic regression model. To validate our findings, we utilized patient-derived organoids and tumor fragments to confirm the associations observed between genetic interactions and drug response. Results: Through integrated analysis of genomics, transcriptomics, proteomics, and metabolomics, we constructed a network comprising 54 co-occurring events and 38 mutually exclusive events, elucidating their association with dysregulated biological processes. External validations were performed in TCGA-BRCA, MSK-IMPACT, METABRIC, and AACR-GENIE datasets, respectively. Furthermore, we systematically revealed the prognostic effects of genetic interactions across distinct clinical subtypes. In triple-negative breast cancer, we found that the co-occurrence of PIK3CAmut-FOXA1mut was associated with unfavorable distant metastasis-free survival while TP53mut-MYBamp and TP53mut-CCNE1amp were associated with decreased overall survival. Additionally, we characterized the genetic interactions that impact the clinical outcomes of patients undergoing specific treatments in the neoadjuvant, adjuvant, and advanced settings. Notably, we identified associations such as TP53mut-AURKAamp with tamoxifen resistance, ERBB2amp-PAK1amp with resistance to trastuzumab-pertuzumab combinations, germline BRCA1mut-MYCamp with sensitivity to PARP1 inhibitors, and TP53mut-MYBamp with immunotherapy resistance. Conclusion: Overall, the consideration of genetic interactions may enhance our understanding of the heterogeneity in treatment response and complement ongoing efforts in precision oncology. Our study suggests that decision-making regarding genome-informed and genome-targeted treatment should extend beyond the scope of single driver alterations. Citation Format: Caijin Lin, Xi Jin, Ding Ma, Chao Chen, Xin Hu, Yi-Zhou Jiang, Zhi-Ming Shao. Comprehensive characterization of genetic interactions in breast cancer reveals therapeutic vulnerabilities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-02.
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Zhu, Xiu-Zhi, Xi Jin, Hu-Yun-Long Zhang, Xiyu Liu, Yi-Fan Zhou, Yi-Yu Chen, Tong Fu, et al. "Abstract PO1-15-07: Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO1–15–07—PO1–15–07. http://dx.doi.org/10.1158/1538-7445.sabcs23-po1-15-07.
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Abstract Background: The standard approach of using one-size-fits-all endocrine therapy for hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancers has faced significant challenges due to variations in treatment response among individuals. Consequently, there is still an urgent need to understand the molecular biology of HR+/HER2- breast cancer and explore precision treatment strategy. Methods: We established a multiomics cohort (n = 351), multicenter real-world clinical cohorts (n = 643), a prospective clinical cohort (MULAN trial), and a drug-testing platform containing patient-derived organoids (n = 126) and patient-derived tumor fragments (n = 49) of HR+/HER2- breast cancers. Integrating "bench" and “bedside” data, we conducted comprehensive preclinical and clinical translational research on precision strategies in HR+/HER2- breast cancer. Results: We implemented a comprehensive classification system for HR+/HER2- breast cancer, comprising four distinct subtypes. We further demonstrated the efficacy and mechanisms of subtyping-directed precision treatment strategies through clinical cohort studies, omics analysis and functional assays: endocrine therapy alone for the canonical luminal subtype; the addition of CDK4/6 inhibitor and PARP inhibitor for the proliferative subtype; the immunotherapy for the immunogenic subtype; and tyrosine kinase inhibitors for the receptor tyrosine kinase-driven subtype. Using clinically applicable subtyping methods, we validated that matched precision treatment strategies outperformed unmatched approaches in a real-world cohort, almost doubling the median progression-free survival time for patients with refractory advanced HR+/HER2- breast cancer (9.83 months [95% CI, 5.74-13.93] vs 4.77 months [95% CI, 3.35-6.18]; hazard ratio 0.64 [95% CI, 0.41-0.99]). Importantly, the first-stage analysis of the MULAN phase II umbrella clinical trial (NCT04355858) verified the higher objective response rate (88.9%, 95%CI: 51.7%-99.7%) of the subtyping-directed precision treatment. Conclusion: Our study emphasizes the superiority of subtyping-directed precision treatment strategies for HR+/HER2- breast cancer, refines traditional “one-size-fits-all” therapy, and facilitates the translation of precision treatment strategies from bench to bedside. Overall study design Part 1 Subtype Molecular Characteristics: Molecular features of the four subtypes of HR+/HER2- breast cancer. Part 2 Multidimensional Efficacy Validation: Integrating data from a multiomics cohort, real-world study, drug testing platform and prospective clinical research to validate the subtyping-directed precision treatment strategy in HR+/HER2- breast cancer. Part 3 Subtyping-directed Precision Treatment Strategy: Integrating clinical cohort studies, omics analysis and functional assays revealed the heterogeneity of treatment response in HR+/HER2- breast cancer, and proposed a subtyping-directed precision treatment strategy. CIN, chromosomal instability; RTK, receptor tyrosine kinase; CNA, copy-number alteration; ER, estrogen receptor; HR, hormone receptor; HER2, human epidermal growth factor receptor 2. Citation Format: Xiu-Zhi Zhu, Xi Jin, Hu-Yun-Long Zhang, Xiyu Liu, Yi-Fan Zhou, Yi-Yu Chen, Tong Fu, Ming-Liang Jin, Ya-Xin Zhao, Yi-Fan Xie, Ruo-Xi Wang, Zhong-Hua Wang, Lei Fan, Yi-Zhou Jiang, Zhi-Ming Shao. Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-07.
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Man, Ki-Fong, Lei Zhou, Ying-Tung Lam, Jun Yu, Jing-Ping Yun, Xin-Yuan Guan, Ming Liu, and Stephanie Ma. "Abstract 5799: SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma." Cancer Research 83, no. 7_Supplement (April 4, 2023): 5799. http://dx.doi.org/10.1158/1538-7445.am2023-5799.
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Abstract Intratumor molecular heterogeneity of hepatocellular carcinoma (HCC) is partly attributed to the presence of cancer stem cells (CSCs), which we now know represents a critical root of tumor recurrence and chemotherapy resistance. CD133 is known to represent an important functional marker of liver CSCs. We have demonstrated CD133 to enrich following chemotherapy treatment, while CD133/Prom1-depletion would enhance sensitivity of HCC tumors to chemotherapy. Yet unfortunately, CD133 is not specific to HCC, but is also expressed in normal regenerating liver. Identifying critical factors expressed specifically in liver CD133+ CSCs, but not in liver normal CD133+ stem/progenitor cells may offer important therapeutic opportunities overcoming chemoresistance in HCC. RNA-seq profiling comparing sorted CD133+ and CD133- subsets of normal regenerating liver induced by DDC diet and HCC induced by either N-nitrosodiethylamine (DEN)/carbon tetrachloride (CCl4) or hydrodynamic tail vein injection of oncogenic plasmids AKT and NRAS identified Serine Peptidase Inhibitor Kazal Type I (SPINK1) to be distinctly expressed in the HCC CD133+ subpopulation but not in normal regenerating liver CD133+ subpopulation. SPINK1 overexpression in HCC clinical samples is correlated with a poor prognosis. Expression of SPINK1 increased during early liver progenitor development, peaked during the premature hepatocyte stage, decreased during hepatocyte maturation and increased progressively from well-differentiated to poorly differentiated HCCs. Enhanced transcriptional activity of SPINK1 was mediated by promoter binding of the epithelial cell-specific transcription factor ELF3, which like CD133, were both increased following chemotherapy treatment. SPINK1 inhibition by lentiviral-based knockdown or a specific monoclonal antibody (mAb) mitigated tumor initiation, self-renewal and chemoresistance. Mechanistically, secretory SPINK1 bound to epidermal growth factor receptor (EGFR) activating MEK/ERK signaling and consequently promoting the formation of CDK4/6-cyclin D1 complex to phosphorylate Rb and release E2F2, allowing the cells to overcome G1/S checkpoint promoting cell cycle progression as well as transcribing stemness, oncogenic dedifferentiation and chemoresistance-related genes. Collectively, our findings suggest SPINK1 to play a critical role in hepatocarcinogenesis and that SPINK1 mAb may represent a novel therapeutic option for the treatment of HCC, targeting at the CD133+ CSC tumor roots and overcoming chemoresistance. Citation Format: Ki-Fong Man, Lei Zhou, Ying-Tung Lam, Jun Yu, Jing-Ping Yun, Xin-Yuan Guan, Ming Liu, Stephanie Ma. SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5799.
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Aberin, Marvin A., Yu-Ling (Pony) Lee, Xin-Guo Hsu, Chen-Yang Shen, Yao-Ming Chang, Kun-Yuan Lin, Chandan Guha, and Shu-Ping Wang. "Abstract 3646: New functional role of tamoxifen in breast cancer immunomodulation: role of RACK7 in activation of type I interferon signaling and CEACAM1/TIM-3-dependent immunosuppression." Cancer Research 83, no. 7_Supplement (April 4, 2023): 3646. http://dx.doi.org/10.1158/1538-7445.am2023-3646.
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Abstract Despite advancements of immunotherapy against various cancers, breast cancer still retains poor response to immune checkpoint blockade (ICB) therapy. Therefore, the identification of promising target or new strategy to enhance ICB therapy in breast cancer is crucial. Here, we uncover that the DNA-damaging potential of tamoxifen (TAM) can shape the unfavorable but ready-to-fire tumor immune microenvironment in breast cancer. We discover that a long-term TAM administration unexpectedly induces JAK/STAT signaling and Type I interferon (IFN)-stimulated gene expression to promote T-cell infiltration. Furthermore, TAM also induces the expression of CEACAM1, which acts as an alternative T-cell inhibitory ligand via binding to TIM-3, a “checkpoint” receptor expressed on CD4+ and CD8+ T cells. The chromatin ‘‘reader’’ RACK7/ZMYND8, which functions as a transcriptional repressor of IFN-stimulated gene (ISG) and a critical factor in DNA repair, is found to be downregulated upon tamoxifen exposure and involved in the tamoxifen-mediated cellular modulation. We demonstrate that TAM in conjunction with RACK7-knockdown (KD) triggers robust upregulation of ISGs and CEACAM1 in both estrogen receptor-positive (ER+) and triple negative breast cancer (TNBC) cells. This immunomodulatory effect lead by loss of RACK7 is specific to TAM treatment, and is not observed when combined with other endocrine therapeutics. TAM combined with RACK7-KD promotes mitochondrial DNA damage, which leads to accumulation of cytosolic DNA and subsequent activation of the cGAS/STING pathway. The murine breast orthotopic models with TS/A, EO771 and 4T1 cells further demonstrate that TAM-mediated immunomodulatory in conjunction with RACK7-KD evokes cytokine/chemokine secretion and further induces T-cell infiltration into tumor microenvironment. However, the tumor killing effect is limited due to promotion of T-cell exhaustion from CEACAM1-TIM-3 interaction between tumor and T cells. Thus, our study indicates that targeting CEACAM1-TIM-3 interaction is crucial for TAM-mediated tumor immune response. This brings promising therapeutic approach with TAM by combining RACK7-KD with blockage to CEACAM1-TIM-3 interaction in breast cancer. The resistance of tamoxifen treatment may be overcome, and RACK7 may serve as both a therapeutic target and a biomarker to enable ICB therapy. Citation Format: Marvin A. Aberin, Yu-Ling (Pony) Lee, Xin-Guo Hsu, Chen-Yang Shen, Yao-Ming Chang, Kun-Yuan Lin, Chandan Guha, Shu-Ping Wang. New functional role of tamoxifen in breast cancer immunomodulation: role of RACK7 in activation of type I interferon signaling and CEACAM1/TIM-3-dependent immunosuppression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3646.
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Ng, Kai-Yu, Tin-Yan Koo, Tsz-Lok Fong, Ya Gao, Tin-Lok Wong, Yuan Gao, Jing-Ping Yun, et al. "Abstract 5437: Chemoproteomics-enabled discovery of covalent inhibitors targeted at AGPAT4: Unravelling tumor lineage plasticity to overcome drug resistance in hepatocellular carcinoma." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5437. http://dx.doi.org/10.1158/1538-7445.am2024-5437.
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Abstract The liver is a unique organ that is responsible for many metabolic functions. During hepatocellular carcinoma (HCC) development, these metabolic machineries are extensively reprogrammed to support the insatiable nutrient requirements of HCC. Tumor lineage plasticity, a recognized hallmark of cancer, is a phenomenon in which tumor cells co-opt developmental pathways to attain cellular plasticity, enabling them to evade targeted therapeutic interventions. Cancer cells can reprogram their metabolic pathways to match their increased metabolic needs for cancer cell survival under adverse conditions. Identifying novel metabolic targets related to stemness can offer promising strategies for targeting cancer stemness roots and hence to kill and control their growth. Through pathway enrichment analysis of genes that linked metabolism and stemness, we identified an aberrant glycerophospholipid metabolism signature, with AGPAT4 ranking as the top-hit. AGPAT4 upregulation in HCC is strongly correlated with aggressive clinical features, including survival, metastasis, and stemness signatures. AGPAT4 expression peaked during early liver progenitor development, decreased during hepatocyte maturation and progressively increased from well-differentiated to poorly differentiated HCCs. Enrichment of AGPAT4 in HCC is mediated by promoter binding of SOX9 to drive AGPAT4 transcriptional activity. AGPAT4 inhibition can mitigate tumor initiation, self-renewal, metastasis, and sorafenib resistance. Mechanistic studies revealed an AGPAT4-mediated phosphatidic acid production axis that promotes HCC through the regulation of mTOR signaling. Inhibition of Agpat4 by AAV8 shRNA reduced tumorigenicity and stemness, and sensitized HCC tumors to sorafenib. AGPAT4 overexpression can predict sorafenib response in clinical settings. Through chemoproteomics screening of a cysteine-reacting compound library using activity-based protein profiling, a cysteine-reacting compound with high binding affinity and selectivity towards AGPAT4 was identified and found to work synergistically with sorafenib to suppress HCC, as demonstrated in HCC patient-derived tumor xenograft (PDTX) models. Toxicity analysis through histological examination of organs, body weight measurements, and biochemical tests revealed minimal toxicity associated with the covalent inhibitor. In conclusion, AGPAT4 is a novel metabolic driver of oncogenic stemness, dedifferentiation, and metastasis in HCC. AGPAT4-induced tumor lineage plasticity may represent an Achilles heel for HCC treatment, and inhibition of AGPAT4 may widen the therapeutic window for sorafenib treatment in the clinic. Citation Format: Kai-Yu Ng, Tin-Yan Koo, Tsz-Lok Fong, Ya Gao, Tin-Lok Wong, Yuan Gao, Jing-Ping Yun, Xin-Yuan Guan, Ming Liu, Clive YS Chung, Stephanie Ma. Chemoproteomics-enabled discovery of covalent inhibitors targeted at AGPAT4: Unravelling tumor lineage plasticity to overcome drug resistance in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5437.
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Mak, Celia Sze Ling, Xin Liang, Jessica Suh, Derek Liang, Ming Zhu, and Guocan Wang. "Abstract 1803: ACOD1 is a key regulator of immunosuppressive MDSCs, prostate cancer progression, and resistance to immunotherapy." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1803. http://dx.doi.org/10.1158/1538-7445.am2024-1803.
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Abstract Although Immune checkpoint therapy (ICT) is highly effective in a wide range of malignancies, patients with metastatic castration-resistant prostate cancer (mCRPC) are largely resistant to ICT. Yet, the cellular and molecular basis of the poor response to ICT in lethal prostate cancer remain poorly defined. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have emerged as a key driver of prostate cancer progression and resistance to immunotherapy. Yet the molecular mechanisms underlying the immunosuppressive activities of PMN-MDSCs remains poorly defined. By performing single-cell RNA-sequencing (scRNA-seq) of prostate tumors, we identified Acod1, a gene that encodes cis-aconitate decarboxylase (ACOD1) and catalyzes the synthesis of itaconate from cis-aconitate in the tricarboxylic acid (TCA) cycle, is among the top 5 metabolic-related genes that are overexpressed in PMN-MDSCs. Moreover, bulk RNA-seq and microarray datasets revealed that intratumoral and splenic PMN-MDSCs express a significantly higher level of Acod1 compared to less immunosuppressive bone marrow PMN-MDSCs. Importantly, high ACOD1 expression is strongly associated with significantly shorter overall survival and higher Gleason scores in human mCRPC. Using an autochthonous whole-body Acod1-KO mouse model, we showed that Acod1 KO in TRAMP mice led to a reduction in tumor burden and an increase in overall survival. Furthermore, using syngeneic prostate cancer models, we showed that whole-body or PMN-specific Acod1-KO delayed tumor progression. As expected, Acod1 KO dramatically reduced the production of itaconate in bone marrow-derived MDSCs (BM-MDSC) as shown by targeted metabolic profiling. Importantly, we found that Acod1 KO impaired immunosuppressive activities of BM-MDSC and an increase in CD3+ and CD8+ T cell infiltration in the tumors. Also, Acod1-KO in BM-MDSC led to a reduction of H2DCFDA staining intensity suggesting a reduction in the production of reactive oxygen species (ROS). Gene set enrichment analysis (GSEA) revealed that Acod1-KO MDSCs have hyperactive oxidative phosphorylation (OXPHOS) compared to Acod1-WT BM-MDSCs. KO of Acod1 also leads to suppression of key MDSC functions signaling such as TNFα/NFκB, IL6/JAK/STAT3, and C/EBPβ pathways. In summary, our data suggests that the upregulation of ACOD1 in PMN-MDSCs has a vital role in prostate cancer progression and resistance to ICT by regulating their immunosuppressive activities through metabolic reprogramming. Also, our data suggest that targeting ACOD1 could be an effective therapeutic strategy for lethal prostate cancer as a monotherapy and in combination with immunotherapy. Citation Format: Celia Sze Ling Mak, Xin Liang, Jessica Suh, Derek Liang, Ming Zhu, Guocan Wang. ACOD1 is a key regulator of immunosuppressive MDSCs, prostate cancer progression, and resistance to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1803.
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Kan, Weiyue. "Yan wei xin sheng: Ming Qing shidai nüxing shengyin yu nanxing qigai zhi jiangou 言為心聲:明清時代女性聲音 與男性氣概之建構 (A study of women’s voices in constructing masculinities in Ming-Qing China), written by Yu Hin Kelvin Ho (He Yuxuan) 何宇軒." NAN NÜ 24, no. 1 (June 9, 2022): 166–69. http://dx.doi.org/10.1163/15685268-02410041.
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Luo, Jie, Lanqi Gong, Yuma Yang, Jiao Huang, Xiaona Fang, Baifeng Zhang, Ying Tang, et al. "Abstract 6064: ADAR1-dependent RNA editing of GLI1 drives hepatocellular carcinoma stem cell self-renewal by initiating mitophagy." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6064. http://dx.doi.org/10.1158/1538-7445.am2022-6064.
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Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common and most difficult to cure malignancies worldwide. Identifying new effective therapeutic targets is of great significance for the management of HCC. Cumulative evidence suggests cancer stem cells (CSCs) are key drivers of tumor growth and heterogeneity. Post-transcriptional RNA editing of adenosine to inosine (A-to-I) catalyzed by ADAR1 dramatically alters cellular transcriptome in cancers. However, ADAR1 editase-dependent mechanisms governing hepatic CSC generation have not been elucidated. Therefore, we have systematically and comprehensively investigated ADAR1’s effect on CSC self-renewal in HCC. Methods: An in vitro human hepatocyte differentiation model along with relevant transcriptomic data form GEO and TCGA were analyzed to characterize the oncofetal role of ADAR1. Using genetic approaches, RNA sequencing was performed to identify putative ADAR1-mediated recoding edited genes in HCC cell lines. Clinical implication of GLI1 editing was studied in a cohort of 88 HCC patients. GLI1 editing-mediated change in its promoter activity and protein stability was investigated by dual reporter assay, CHIP, Co-IP, and PLA assays. Functional difference in stemness properties, including abilities of self-renewal, differentiation, tumorigenesis, chemo-resistance and metastasis between wild-type and edited GLI1 (GLI1wt vs. GLI1R701G) and the exact mechanisms were also studied in cell models and mice. Results: Lentiviral ADAR1 wild-type but not editing-defective ADAR1E912A mutant, editing at nt2101 of GLI1 transcript caused arginine-to-glycine substitution at the residue 701. Importantly, increased editing of GLI1 was implicated in the pathogenesis of HCC. Upon editing, C-terminal half of GLI1 harbored a lower susceptibility to the inhibition of SUFU, thus promoting its nuclear translocation and activation. Moreover, GLI1R701G appeared more stable than GLI1wt due to reduced formation of specific K63-GLI1 substrate and β-TrCP-GLI1 complex. Edited GLI1 was found to strongly enhance targeted activation of NANOG and SOX9, resulting in accumulation of hepatic CSCs population, hepatocarcinogenesis, sorafenib-resistance and metastasis. Additionally, GLI1 editing initiated mitophagy via PINK1/Parkin-dependent pathway. Impaired mitophagy effectively antagonized the functions of GLI1R701G on hepatic CSC self-renewal and overcome chemoresistance. Conclusion: The critical advance of this study is that ADAR1 editase activity drives GLI1-dependent maintenance of the hepatic CSC population. Our discovery of a pivotal ADAR1-GLI1-PINK1 self-renewal axis provides the first mechanistic link between RNA-editing-driven malignant progression and mitochondrial homeostasis. Thus, ADAR1 represents a unique therapeutic vulnerability in liver CSCs with active mitophagy mediated by edited GLI1. Citation Format: Jie Luo, Lanqi Gong, Yuma Yang, Jiao Huang, Xiaona Fang, Baifeng Zhang, Ying Tang, Beilei Liu, Ming Liu, Lu Bai, Victor Ho-Fun Lee, Xin-Yuan Guan. ADAR1-dependent RNA editing of GLI1 drives hepatocellular carcinoma stem cell self-renewal by initiating mitophagy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6064.
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Cheng, Yong, Ming-Jian Ge, Peng Dong, Yan-Yu Qiu, Xin-Peng Shu, Jin-Dou Li, Jun-Wei Wang, and Xiao-Fang Qi. "Abstract 5133: Genetic characteristics & clonal evolution of Chinese resectable colorectal cancer patients with lung metastases." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5133. http://dx.doi.org/10.1158/1538-7445.am2022-5133.
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Abstract Background Colorectal cancer (CRC) has a high incidence and mortality. In CRC, the lung is the most common extra-abdominal site of metastasis. Understanding the genetic characteristics and clonal evolution of primary tumor and lung metastases (LM) will help oncologists better outline treatments. To date, few studies for CRC with LM exist. As such, revealing the genetic characteristics and clonal evolution of resectable CRC with LM was the goal of this study. Methods From January 2012 to July 2019, clinical data and formalin-fixed, paraffin-embedded samples were collected from 33 Chinese CRC patients. Nineteen (19) primary tumors and 10 matched LM samples were examined using a 450 cancer gene next-generation sequencing assay. Genomic alterations, including single base substitutions, indels, copy number variations (CNVs), and gene fusion and rearrangement, were assessed. A phylogenetic reconstruction of sequencing data using LICHeE was also performed for each patient. Results Median patient age was 60 years old (48-67 years), with most having right lung metastasis. A significant difference existed between single (21/33, 63.6%) and multiple LM (12/33, 36.4%) (P < 0.01). Median disease-free survival was 20 months (95% CI, 0-84), from primary CRC to LM. The most frequently mutated genes were TP53 (90%), APC (90%), KRAS (53%), MUC16 (26%), ARID1A (21%). A comparison of mutational profiles for primary and matched LM samples revealed that 65.70% of alterations were consistent and that the most frequently mutated genes, including APC, TP53, and KRAS, of the primary tumor were completely consistent with LM. However, some differences between metastatic and primary samples were determined. More CNVs were found in primary samples (11.4% vs. 4.6%), indicating that CNVs are early molecular events for tumorigenesis and disease progression. SMAD4 was only present in two primary samples, while LRP1B was only present in two LM samples. Clonal evolution for eight patients indicated that phylogenetic structure was similar across patients. All patients had at least seven mutations on trunks. In trunks, TP53 (87.5%), APC (87.5%), KRAS (50%), and LRP2 (37.5%) were frequently identified. A new actionable gene (BRCA2) emerged in LM sample was identified in one patient. The mean value of TMB for the primary was almost the same as that for the LM site (5.3 vs. 5 muts/Mb, P > 0.05). Conclusions Our data indicated that the genetic characteristics and clonal evolution of LM are highly consistent with those of the primary tumor, suggesting that suitable treatments can be selected based on the genetic characteristics of primary tumor in CRC patients with LM that cannot be surgically treated. Citation Format: Yong Cheng, Ming-Jian Ge, Peng Dong, Yan-Yu Qiu, Xin-Peng Shu, Jin-Dou Li, Jun-Wei Wang, Xiao-Fang Qi. Genetic characteristics & clonal evolution of Chinese resectable colorectal cancer patients with lung metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5133.
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Liu, Puning. "The Adoption of Neo-Confucianism in Discussing Legitimacy Dispute." Asian Culture and History 10, no. 1 (December 8, 2017): 43. http://dx.doi.org/10.5539/ach.v10n1p43.
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Lipset (1960) denotes legitimacy as “the capacity of the system to engender and maintain the belief that the existing political institutions are the most appropriate ones for the society.” All political powers, including Chinese dynasties in history, needed legitimacy to ensure their governance. In general, Western thinkers who discuss political legitimacy could be identified into two groups (Habermas, 1979). The “empiricists”, likes Max Weber, studies legitimacy in an empirical method, focusing on the types, constitutions, functions, and evolutions of legitimacy. The second group consists of “normativists”, such as Plato and John Rawls, who tend to base legitimacy on various normative values such as justice or democracy. Pre-modern Chinese views on political legitimacy have the similar approaches like west. The first one pays attention to different empirical factors of legitimacy. For instance, the pre-Qin philosopher Zou Yan (305-240 BCE), and Western Han thinker Liu Xin (50 BCE-23 CE) view a dynasty’s legitimate by its adoption of rightful dynastic phase (Wang 2006). The Song Dynasty (960–1279) historian Ouyang Xiu (1007-1072) argues that the just position and the unification of China make a legitimate dynasty (Rao 1996). The second approach bases legitimacy on normative values. For example, Confucius (551-479 BCE) indicates that the rightfulness of a ruler relies on his properly practicing both “benevolence” (ren ), and “rites” (li ). Many present scholars give us their studies on the legitimacy in Chinese history. For instance, Rao Zong (1996) provides the general overviews of legitimacy in the Chinese tradition, with an extensive collection of relevant primary sources. Hou Deren (2009) introduces most relevant present-day Chinese studies on that issue. For English readers, general studies of traditional Chinese views on legitimacy can be found in the writings of Hok-lam Chan (1984) and Richard Davis (1983). Nevertheless, it is notable that the question of legitimacy became pressing from the 13th century onwards in China, when China was ruled by non-Chinese ruling houses, such as the Yuan Dynasty 元 (1272-1368) and Qing Dynasty (1889-1912). Scholars during that period showed a great interest in discussing the question of what makes a legitimate ruler of China. In general, these scholars approached that question in two ways; they introduced the prevailing Neo-Confucianism to define the virtuous rule as the principal value of legitimacy (Bol, 2009), or they defined a Chinese ruled dynasty as legitimate. To reveal these scholars’ distinct views on legitimacy, this paper investigates two of them, the Yuan literatus Yang Weizhen (1296-1370) and the Ming (1368-1644) scholar-official Fang Xiaoru (1357-1402). For English readers, only Richard Davis (1983) gives a brief introduction on Yang Weizhen’s views on legitimacy. Few studies focus on Fang Xiaoru’s relevant views. Following the text analysis way, this article proves that Yang Weizhen and Fang Xiaoru acted as two representatives of scholars in the late imperial China. Both of them adopted Neo-Confucianism to discuss legitimacy, viewing the discussion of legitimacy as a moral evaluation of the dynasty and monarch. They also shared the idea that Chinese ruled dynasty should be viewed as legitimate.
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Huang, Furong, Fuwen Yuan, Ya Cui, Lei Li, Kexin Li, Zhifen Cui, Jingyue Yan, et al. "Abstract 5359: Targeted engineering mRNA 3′UTR length enhances immunotherapy response in prostate cancer." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5359. http://dx.doi.org/10.1158/1538-7445.am2024-5359.
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Abstract Background: Global mRNA 3′untranslated region (3′UTR) shortening through alternative polyadenylation (APA) has been widely observed in most cancers; however, it has not been demonstrated whether targeted interference of specific oncogenic mRNA 3′UTR lengths can inhibit tumor growth and potentiate immunotherapy response in prostate cancer. Methods: DaPars algorithm was applied for de novo identification of dynamic alternative polyadenylation (APA) during prostate cancer progression to the lethal phase; 3′UTR polyadenylation site (PAS) locations and usages were identified by Poly(A)-ClickSeq (PAC-seq) and 3′RACE; APA transcripts were quantified by RHAPA assay; a 3′UTR CRISPR/dCas13 Engineering System (3′UTRCES) was developed to manipulate the length of desired 3′UTRs; RIP-qPCR and PAR-CLIP-qPCR assays were used to determine the mechanistic basis of 3′UTRCES in APA editing; RNA-seq was utilized to evaluate the off-target effects; TT3 Lipid-like nanoparticles (LLN) were applied for intratumoral delivery of 3′UTRCES RNA molecules for targeted 3′UTR therapy. Quantitative proteomics and immunoprecipitation assays were conducted to investigate how major histocompatibility complex class I (MHC-I) substrates were recognized by SPSB1-containing ubiquitin ligase complex for degradation; Flow cytometry and T cell cytotoxicity assays were performed to evaluate MHC-I level and killing of tumor cells by antigen-stimulated CD8+ T cells. Results: 3′UTR globally shortens during prostate cancer progression to castration-resistance. Through blocking the proximal PASs, 3′UTRCES efficiently and specifically reverses the 3′UTR shortening of novel APA-linked, clinically-relevant prostate cancer oncogenic mRNAs, such as SPSB1, leading to reduced SPSB1 mRNA translation and prostate cancer cell proliferation. Intratumoral injection of TT3 LLN encapsulating 3′UTRCES RNA molecules effectively and safely inhibits prostate tumor growth in engrafted and transgenic mouse models. Notably, downregulation of SPSB1 protein by 3′UTRCES disrupts the interactions of SPSB1-containing ubiquitin ligase complex, leading to compromised ubiquitination-mediated MHC-I degradation and increased stability and abundance of MHC-I protein. Consistently, 3′UTRCES enhances MHC-I-regulated antigen presentation and thereby augments CD8+ T cell-mediated cytotoxicity, which suggest the potentials of 3′UTRCES to sensitize prostate cancer to immune checkpoint therapies. Importantly, 3′UTR shortening of SPSB1 mRNA is significantly associated with decreased MHC-I expression, reduced cytotoxic T-cell infiltration and activation in castration resistant prostate cancer patients. Conclusions: Our results establish the concept of “3′UTR targeted therapy” for treatment of prostate cancer with broad applications to other cancers and other 3′UTR-related diseases. Citation Format: Furong Huang, Fuwen Yuan, Ya Cui, Lei Li, Kexin Li, Zhifen Cui, Jingyue Yan, Qiang Chen, Christopher Nicchitta, Wenbin Ye, Yuebao Zhang, William Hankey, Jeffrey Everitt, Ming Chen, Jiaoti Huang, Hongyan Wang, Xin Lu, Eric Wagner, Yizhou Dong, Wei Li, Qianben Wang. Targeted engineering mRNA 3′UTR length enhances immunotherapy response in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5359.
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Xin, Ying, Jiayu Liu, You Qin, Kexing Lyu, Sifei Yu, Ming Lin, Max Wicha, Alfred E. Chang, and Qiao Li. "Abstract 2256: Cancer stem cells and exosomal PD-L1 suppress anti-tumor B cells." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2256. http://dx.doi.org/10.1158/1538-7445.am2023-2256.
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Abstract We have conducted clinical trials for cancer immunotherapy using vaccine-primed lymph node (VPLN) T calls based on our animal studies with tumor-draining lymph node (TDLN) T cells. More recently we have identified antitumor effector TDLN B cells which demonstrated significant tumor reactivity in vitro and therapeutic efficacy in vivo upon adoptive transfer which can be enhanced by anti-PD-L1 administration. It is unknown whether tumor cells, particularly cancer stem cells (CSCs) could suppress the antitumor effector B cells. We found that depletion of B cells with anti-CD20 mAb prior to anti-PD-L1 administration resulted in more aggressive tumor growth, and the anti-tumor efficacy of anti-PD-L1 was significantly reduced in both 4T1 and CT26 murine tumor-bearing hosts, suggesting the involvement of host B cells in the anti-tumor effect of anti-PD-L1. In addition, administration of anti-PD-L1 partially recovered the humoral immune response, confirming the PD-L1/PD-1 pathway involvement in B cell suppression. We detected elevated expression of PD-1 on activated B cells, and higher PD-L1 expression on ALDHhigh CSCs than on ALDHlow non-CSCs. Co-culturing ALDHhigh CSCs with purified B cells significantly reduced IgG secretion, and such CSC-mediated B cell suppression was rescued by adding anti-PD-L1 mAb in a dose-dependent manner to the CSC-B cell co-culture. These experiments thus indicate that CSCs suppress the IgG production by B cells via the PD-L1/PD-1 axis. Tumor cells were recently recognized to suppress T cell function via secretion of exosomes that express PD-L1. To investigate if exosomal PD-L1 contributes to B cell immunosuppression, we generated Rab27ako D5 cells to delete exosomes as well as PD-L1ko D5 cells by CRISPR/Cas9 gene editing. D5-derived exosomes suppressed B cell proliferation and IgG production in vitro, and administration of these exosomes promoted tumor growth and reduced animal survival, revealing the role of tumor-derived exosomes in B cell immunosuppression. Tumor-derived exosomes expressed PD-L1, but PD-L1 was absent in the exosomes isolated from the PD-L1ko tumor cells as evident by western blot and flow cytometry. Deletion of Rab27a or PD-L1 did not affect the proliferation of the tumor cells in vitro. However, Rab27ako or PD-L1ko resulted in significantly enhanced host anti-tumor immunity evident by reduced 4T1 tumor growth in vivo compared with the WT tumor. Importantly, anti-PD-L1 therapy significantly reduced Rab27ako or PD-L1ko 4T1 tumor growth and prolonged animal survival vs. the WT tumor control. We conclude that PD-L1-expresing CSCs and PD-L1-expresing exosomes suppress antitumor effector B cells via the PD-L1/PD-1 axis. To characterize the suppression of CSC-derived exosomes on host B cells as well as T cells, isolation of Rab27ako ALDHhigh CSCs warranties further investigation. Citation Format: Ying Xin, Jiayu Liu, You Qin, Kexing Lyu, Sifei Yu, Ming Lin, Max Wicha, Alfred E. Chang, Qiao Li. Cancer stem cells and exosomal PD-L1 suppress anti-tumor B cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2256.
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Gong, Yue, Peng Ji, Huai-liang Wu, Li-Hua He, Ming-Liang Jin, Xin Hu, Yi-Zhou Jiang, and Zhiming Shao. "Abstract PO1-14-06: Integrated analysis reveals the impact of obesity on triple-negative breast cancer." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO1–14–06—PO1–14–06. http://dx.doi.org/10.1158/1538-7445.sabcs23-po1-14-06.
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Abstract Background: Obesity and overweight status, which has been growing rapidly over the past few decades, is considered as a risk factor for many types of cancers including breast cancer. Despite the multi-omics profile of triple-negative breast cancer (TNBC) has been comprehensively characterized, the impact of obesity on molecular features of TNBC is not fully appreciated. Methods: We applied an integrative analysis on clinicopathological data and molecular data (including genomic, transcriptomic, proteomic and metabolomic profiling) using the multi-omics database of TNBC (N = 465) from Fudan University Shanghai Cancer Center (FUSCC) for associations with patient body mass index (BMI). Patients were categorized into overweight/obese (OW/OB, BMI ≥ 24 kg/m2) and normal (NL, BMI < 24 kg/m2) group according to the Chinese criteria of BMI. The clinical and molecular differences between OW/OB and NL patients were systematically explored. We also constructed high-fat diet (HFD)-induced obese mouse tumor models and used single-cell RNA sequencing to investigate the impact of obesity on the tumor microenvironment. Furthermore, we analyzed the efficacy of anti-PD-1 immunotherapy on TNBC tumors in both obese and normal mice. Results: OW/OB patients exhibited higher proportion of metabolic syndrome, more adipose tissue in the breast and worse survival than NL patients. Among most frequently mutated genes, OBSCN showed statistically significantly less mutated in the OW/OB group (3.2% vs 9.6%), while TP53 (68.3% vs 76.9%) and PIK3CA (21.4% vs 14.1%) had tendency to be different. In terms of copy number alterations, we found OW/OB patients had a higher amplified or gained frequency of 13q14.11 (FOXO1) and a lower frequency of deletion or loss of chromosomal region 7p22.1 (FOXK1). We further dissect the expression profile of TNBC. Differentially expressed gene analysis and pathway enrichment analysis demonstrated that immune and metabolic pathways were the major distinction between OW/OB and NL tumors. OW/OB tumors were characterized with elevated inflammation of tumor microenvironment, as well as higher expression of immune checkpoints. Moreover, analyses focusing on metabolic heterogeneity using transcriptomic, proteomic and metabolomic data revealed upregulation of lipid metabolism and reactive oxygen species pathway in OW/OB group. In addition, our in vivo experiments demonstrated that TNBC in the obese mice displayed faster growth rates. Flow cytometry analysis and single-cell RNA sequencing showed that higher proportion of immunosuppressive myeloid cells and exhausted CD8+ T cells and upregulation of lipid metabolism in HFD group. Applying anti-PD-1 immunotherapy in both obese and normal mice displayed that tumors in the obese mice showed more sensitive to anti-PD-1 immunotherapy. Conclusion: Our study systematically revealed that obesity might play a significant role in the molecular heterogeneity of TNBC and showed distinct sensitivities to immunotherapy, which should be taken in account in the field of precision medicine. Keywords: triple-negative breast cancer, obesity, immune, tumor microenvironment, metabolism Citation Format: Yue Gong, Peng Ji, Huai-liang Wu, Li-Hua He, Ming-Liang Jin, Xin Hu, Yi-Zhou Jiang, Zhiming Shao. Integrated analysis reveals the impact of obesity on triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-14-06.
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Koka, Hela, Xin Li, Difei Wang, Difei Wang, Kristine Jones, Kristine Jones, Aurelie Vogt, et al. "Abstract A040: Cellular ecosystem of breast tumor microenvironment in Chinese breast cancer patients." Cancer Research 84, no. 3_Supplement_1 (February 1, 2024): A040. http://dx.doi.org/10.1158/1538-7445.advbc23-a040.
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Abstract Background: Current evidence has demonstrated the important role of tumor microenvironment (TME) in cancer initiation and progression. However, the dynamic interactions among various cells and their communities in TME remain largely unknown. Recently, EcoTyper, was developed to discover different cell states and their ecosystems in silico using bulk gene expression data. The application of this tool in the Pan-Cancer analysis identified distinct cell states and ecotypes (co-association patterns between cell states) that act as strong classifiers for cancer types and subtypes. In this study, we aimed to discover the TME ecosystems in breast tumors from an East Asian population and associate them with well annotated clinical features and breast cancer (BC) risk factors. Methods: We applied the EcoTyper framework to tumor RNA-Seq data from 242 Hong Kong BC patients to identify carcinoma ecotypes (CEs) and associated them with intrinsic subtype (PAM50), driver gene mutations (based on whole genome/exome sequencing analyses), and well-known BC risk factors. Additionally, we used The Cancer Genome Atlas BC (TCGA-BRCA) data, which was part of the initial EcoTyper Pan-Cancer analysis, as a quality control and comparison dataset. The TCGA patients were predominantly of European ancestry and had similar age distribution (median=58 years) compared to HK patients (median=60 years). The distribution of PAM50 subtype was also similar between the two datasets, with HK having a slightly higher proportion of luminal A (38% vs. 33% in TCGA) and a lower proportion of basal (11% vs. 20% in TCGA). Results: Among all ten ecotypes, the frequency of each CE was very similar between HK and TCGA. In both datasets, the prevalence of these CEs varied by tumor subtype. CE1 and CE6 were enriched in luminal A and rare in basal, while CE9 was rarely found in luminal A but showed high prevalence in HER2-enriched and basal subtypes. CE7 was enriched in luminal B (especially in HK, where among tumors with CE7, 82% of them were luminal B), CE10 was enriched in HER2-enriched (especially in HK, where 41% of tumors with CE10 were HER2-enriched), and CE2 was enriched for basal subtype. CE8 was enriched for luminal A in HK and luminal B in TCGA. The presence of CE2, CE9, or CE10 was associated with higher prevalence of TP53 somatic mutations, particularly in HK. Among the BC risk factors examined, we did not find any statistically significant associations with any CEs, probably due to the small sample size. The work of assessing the associations with the abundance of each cell state and CE is currently ongoing. Conclusions: We replicated cellular ecosystems and their associations with tumor subtypes and driver gene mutations in an East Asian population, demonstrating its generalizability and potential utility in refining BC subtypes. Next, we plan to extend the analysis to paired adjacent normal tissue to further assess the role of these ecosystems in shaping TME heterogeneity and tumor evolution. Citation Format: Hela Koka, Xin Li, Difei Wang, Difei Wang, Kristine Jones, Kristine Jones, Aurelie Vogt, Aurelie Vogt, Bin Zhu, Amy Hutchinson, Amy Hutchinson, Belynda Hicks, Belynda Hicks, Priscilla Ming Yi Lee, Lap Ah Tse, Xiaohong R Yang. Cellular ecosystem of breast tumor microenvironment in Chinese breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A040.
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Dai, Lei-Jie, Ding Ma, Yi Xiao, Xi Jin, Song-Yang Wu, Ya-Xin Zhao, Han Wang, Wen-Tao Yang, Yi-Zhou Jiang, and Zhi-Ming Shao. "Abstract HER2-09: HER2-09 Multiomics Profiling Characterizes Distinct HER2-low Breast Cancer Subgroups in the East Asian Population." Cancer Research 83, no. 5_Supplement (March 1, 2023): HER2–09—HER2–09. http://dx.doi.org/10.1158/1538-7445.sabcs22-her2-09.
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Abstract Background: The emergence of anti-HER2 antibody–drug conjugates (ADCs) gave rise to the concept of HER2-low breast cancer (BC). HER2-low BC, which refers to a subgroup of HER2-negative BC with relatively higher HER2 expression (defined as 1+ or 2+ by immunohistochemistry (IHC) staining, without ERBB2 amplification), represents a rather large part of all BCs. However, the molecular nature and internal heterogeneity of HER2-low breast cancer remain obscure, and little is known about the ethnic differences of HER2-low BC. These limitations prevent us from a more precise patient selection and better drug combination strategies in the era of ADCs. To provide a comprehensive and intensive landscape of HER2-low BCs, we characterized HER2-low BCs both clinically and molecularly, which may help clinicians to achieve a more precise clinical management of these patients. Patients and methods: We established a HER2-low BC cohort (N=441) in early-stage Chinese patients and included HER2-0 (N=114) and HER2-positive (N=181) tumors as auxiliary cohorts to characterize HER2-low breast cancers both clinically and molecularly. Whole-exome sequencing, copy number variation assays, RNA sequencing and isobaric quantitative proteomics were conducted to obtain multiomics data. We compared the clinicopathological and molecular features between HER2-low tumors and other HER2 status subgroups stratified and not stratified hormone receptor (HR) status to clarify the distinctness of HER2-low BCs. And we analyzed the internal heterogeneity and ethnic difference of HER2-low BCs by characterizing a distinct subgroup of patients with unique driving mechanisms. Results: HER2-low BCs showed different molecular manifestations from HER2-0 BCs in different HR subgroups. In the HR-negative subgroup, HER2-low BCs consisted of more non-basal-like subtypes than HER2-0 tumors (40.0% vs. 9.1%, P = 0.002), which was an East Asian-specific phenomenon absent in Western cohorts. Also, HR-negative HER2-low BCs showed significant internal molecular heterogeneity, of which basal-like tumors closely mimicked HER2-0 BCs, whereas non-basal-like tumors were similar to HER2-positive BCs. These non-basal-like tumors were mostly categorized as HER2-enriched and luminal androgen receptor (LAR) subtypes. These molecularly distinct tumors might be driven by frequent mutation in PIK3CA and overexpression of FGFR4 and PTK6, which may also serve as therapeutic targets. These results have also been proved in a triple negative breast cancer cohort we reported previously. In contrast, in the HR-positive subgroup, HER2-low BCs showed no large-scale molecular difference from HER2-0 BCs or internal heterogeneity. However, HER2-low patients showed significantly better distant metastasis-free survival than HER2-0 patients (P = 0.029), which might be attributed to the lower loss/deletion levels of 17q11.12 and 17q21.31 in HER2-low breast cancers, in which genes including NF1 and BRCA1 are located. Conclusions: We reported the largest single-center multiomics HER2-low BC cohort in East Asian hitherto, and revealed its molecular nature, internal heterogeneity and ethnic difference. Compared with HR-positive diseases, HER2-low BCs in the HR-negative subgroup were more likely to be a molecularly distinct entity from HER2-0 tumors. Furthermore, HR-negative HER2-low BC also accommodates higher internal heterogeneity, which was ethnicity-specific in our East Asian cohort and may infer a different treatment response. Our work emphasized the need of a more precise stratification within HER2-low BCs and across ethnic groups, which has also been inferred by the results in the subgroup analysis of DESTINY-Breast04 trial. Citation Format: Lei-Jie Dai, Ding Ma, Yi Xiao, Xi Jin, Song-Yang Wu, Ya-Xin Zhao, Han Wang, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao. HER2-09 Multiomics Profiling Characterizes Distinct HER2-low Breast Cancer Subgroups in the East Asian Population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-09.
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Fan, Lei, Xiyu Liu, Ying Xu, Xinyi Sui, Wenjuan Zhang, Linxiaoxi Ma, Xi Jin, et al. "Abstract PO1-06-12: Phase II study of sitravatinib plus tislelizumab with or without nab-paclitaxel in patients with locally recurrent or metastatic triple negative breast cancer." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO1–06–12—PO1–06–12. http://dx.doi.org/10.1158/1538-7445.sabcs23-po1-06-12.
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Abstract Background: The combination of a PD-(L)1 inhibitor plus chemotherapy demonstrated promising anti-tumor activity as first-line therapy for patients (pts) with locally recurrent inoperable or metastatic PD-L1 positive triple-negative breast cancer (TNBC). However, for pts without PD-L1 expression and for those who have failed prior lines of treatment, therapeutic options are still limited. This multi-cohort, phase II trial aimed to evaluate the safety and antitumor activity of 70 mg (cohort A) or 100 mg (cohort B) sitravatinib plus tislelizumab in pts with locally recurrent or metastatic TNBC, and their combination (70 mg sitravatinib plus tislelizumab) with nab-paclitaxel in untreated locally recurrent inoperable or metastatic TNBC pts (cohort C). The efficacy of sitravatinib plus tislelizumab in cohort A and B has been reported with objective response rate (ORR) of 38.1% and 45.0%, respectively. Herein, the preliminary results of cohort C and updated results of cohort A and B were reported. Methods: Pts with untreated locally inoperable or metastatic TNBC were included in cohort C and received 70 mg sitravatinib orally once daily plus 200 mg tislelizumab intravenously on day 1 and 100mg/m2 nab-paclitaxel on days 1 and 8 every three weeks until disease progression or intolerable toxicity. The primary endpoint was ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), 1-year overall survival (OS) rate and safety/tolerability. Based on Simon’s two-stage design, > 9 responders were need in stage 1 (n=18) for the study to continue, and >19 responders were needed by the end of study (n=35) to demonstrate statistical superiority with sitravatinib plus tislelizumab and nab-paclitaxel (assumed to be around 65%) to a historical control of 46% (1-sided alpha of 0.1, power of 80%). Updated analyses were provided for cohort A (Simon’s 2 stage design) and B (Bayesian optimal phase II design). Results: Among the 18 pts in stage 1 of cohort C, 12 of them achieved confirmed response, and therefore the study proceeded to the enrollment in stage 2. As of April 30, 2023, a total of 32 pts were enrolled, with a median age of 51 years. Among the 23 efficacy evaluable pts, unconfirmed ORR was 87.0% (95% CI 66.4-97.2) (including 3 CRs and 17 PRs), with 7 pts not reaching next tumor assessment after reaching CR/PR, and confirmed ORR was 52.2% (95% CI 30.6-73.2). DCR was 95.7%. Any grade of treatment-related adverse events (TRAEs) occurred in 31 (96.9%) pts, and grade ≥3 TRAEs occurred in 5 (15.6%) pts. One (3.1%) patient experienced grade ≥3 immune-related adverse events. SAEs were reported in 3 (9.4%) pts. At the data cut-off date, the median follow-up duration for cohort A and B was 20.4 (range 1.3–24.3) months and 13.3 (range 5.1-19.1) months, respectively. The median PFS in cohort A was 8.2 (95% CI 2.8-12.4) months, and in cohort B was 5.4 (95% CI 4.2-10.9) months. Median OS was not reached in both cohorts. RNA-seq analysis showed that the suppression of immune regulatory pathways and the activation of metabolic pathways promoted early progression. Besides, baseline angiogenesis associated pathway held the potential to predict the favorable response to tislelizumab plus sitravatinib. Conclusion: In the first-line treatment of locally recurrent or metastatic TNBC, preliminary analysis of cohort C showed that sitravatinib combined with tislelizumab and nab-paclitaxel had promising anti-tumor activity with a high ORR, and the combination was generally well tolerated. In TNBC pts with less than three lines of therapy, the chemotherapy-free regimen with sitravatinib plus tislelizumab demonstrated promising PFS after a longer follow-up duration. Citation Format: Lei Fan, Xiyu Liu, Ying Xu, Xinyi Sui, Wenjuan Zhang, Linxiaoxi Ma, Xi Jin, Song-Yang Wu, Han Wang, Yi Xiao, Li Chen, Jiong Wu, Ke-da Yu, Guangyu Liu, Xin Hu, Zhonghua Wang, Yi-Zhou Jiang, Zhi-Ming Shao. Phase II study of sitravatinib plus tislelizumab with or without nab-paclitaxel in patients with locally recurrent or metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-12.
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Wang, Zuoyue. "Jian Zhang. Ke xue she tuan zai jin dai Zhongguo de ming yun: yi Zhongguo ke xue she wei zhong xin [The Science Association and the Change of Society in Modern China: A Study on the Science Society of China]. (Zhongguo jin xian dai ke xue ji shu shi yan jiu cong shu.). 460 pp., tables, bibl., index. Jinan: Shandong jiao yu chu ban she [Shandong Education Press], 2005. ¥49 (paper)." Isis 99, no. 2 (June 2008): 437–38. http://dx.doi.org/10.1086/591376.
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"Correction." Journal of Historical Research in Music Education 30, no. 1 (October 2008): 3. http://dx.doi.org/10.1177/153660060803000102.
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In the last issue (Vol. 29, No.2), there was a mistake in Wai-Tong Lau's article, “Songs Tied onto the Chariot—Revolutionary Songs of the Cultural Revolution in China (1966–1976)” on page 106. JHRME regrets the inaccuracies. The corrected paragraph reads as follows: A number of revolutionary songs of the Cultural Revolution are written in the musical styles of the Chinese minorities. “The Great Beijing” (Wei Da De Beijing by Nu Er Mai Mai Ti), a song written by a Xinjiang composer, was very popular during the Cultural Revolution. This song is filled with syncopated rhythm typical of the Xinjiang minority dances. Another classic revolutionary song of the Cultural Revolution, “A Song within My Heart for the People's Liberation Army” (Wo Xin Zhong De Ge Xian Gei Jie Fang Jun by Chang Liuzhu), composed by a Han composer, is written with rhythmic patterns characteristic of the Tibetan dances. Other similar songs are one for the Bei Minority, “Never-Ending Singing of the Zhan Mountain” (Zhan Shan Ge Sheng Yong Bu Luo by Zhang Wen); one for the Korean minority, “Yanbian People Love Chairman Mao” (Yanbian Ren Ming Re Ai Mao Zhu Xi by Jin Fenghao); one for the Zhuang minority, “Zhuang People Sing for Chairman Mao” (Zhaung Zu Ren Ming Ge Chang Mao Zhu Xi by the Creation Group of the Department of Culture of Guangxi Zhaung Autonomous Region); and one for the Wa minority, “Ah Wa People Sing New Songs” (Ah Wa Ren Ming Chang in Ge by Yang Zhengren). These revolutionary songs of the minorities enriched the genre of revolutionary songs of the Cultural Revolution with a variety of rhythmic and tonal idioms different from those of the mainstream Han music.
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Zhou, Xiaojing. "Migration, Displacement, and Movements in the Global Space: Ming-Yuen S. Ma’s Multi-Media Project Xin Lu: A Travelogue in Four Parts." Journal of Transnational American Studies 4, no. 1 (2012). http://dx.doi.org/10.5070/t841012822.
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O'Connor, Katie. "Art and Identity in the Forbidden City." Spectrum, no. 10 (May 25, 2023). http://dx.doi.org/10.29173/spectrum182.
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By representing and manipulating locations that hold widespread cultural significance, artists mediate the relationship between individuals and city spaces. The photographic work of Cui Xiuwen explores the complexity of identity formation in the Forbidden City, the political center of China. Studying the nuances of her piece One Day in 2004 No. 6 reveals the tension of the relationship between the body and the spaces it inhabits. Though Cui has emphasized the dominating presence of Tiananmen Gate looming over her youthful female figure, the image also supports the agency of this young girl. Rather than defining the piece as a representation of either subordination to the weight of cultural history or the assertion of individual identity, this paper recognizes the paradox inherent in the work. In my analysis of the photographic image, I embrace contradictory readings of its meaning to emphasize the importance of visual culture in how individuals define themselves in city spaces. The paper draws on the shifting cultural meaning of Tiananmen Gate and contextualizes Cui’s work with pieces by other contemporary Chinese artists, including Hu Ming and Lin Xin, engaging in similar themes. Analyzing specific elements of Cui’s piece, such as the Young Pioneer’s Uniform and the young girl’s cyborg hand, reveals the significance of gender when considering identity formation in the Forbidden City. This paper outlines the subtleties of Cui’s artwork to place it in conversation with academic and artistic representations of the Forbidden City, as the historical significance of this space continues to influence self-conception.